We propose to study the chemistry, genetics, immunology and physiology of Ia antigenic specificities secreted into serum in a murine model and in man. The studies of others have defined the Ia specificities within the murine H-2 complex and have demonstrated the importance of these specificities in the MLR, in T-B cell co-operation and in graft rejection. Our studies have already demonstrated Ia substances in serum and that these can be detected by a rabbit antiserum as well as by the conventional alloantibodies. We have also shown that Ia substances of low molecular weight are secreted by helper T cells after contact with antigen, and this material is predominantly carbohydrate. We have also made substantial progress with this model in man. We now intend to study in the murine Ia model: (a) the carbohydrate chemistry of the Ia specificities: structure of high molecular weight and low molecular weight components and further chemical analysis using enzyme studies (b) examine secretion in tumor bearing mice (in allogenic and syngeneic recipients) and after treatment with carcinogenic agents (c) examine the secretion in rats undergoing renal allograft rejection (d) examine secretion in mice under circumstances to determine the specificity of Ia secreted and its relation to antigenic stimulation (e) to determine, in a GVH model, the genetic control of the secretion of I region specificities. We also intend to further our genetic studies of H (Ia) - the human equivalent to the Ia specificities - and to exploit the demonstrated homologies between murine and human Ia to study the chemistry, immunology and physiology of Ia secretion in man. In particular we wish to determine whether the measurement of Ia levels is equivalent to monitoring T cell function. Thus far, it seems that it does, but two circumstances require intensive study (a) the rejection of human renal allografts (b) examination of cancer patients to serum for tumors which may well suppress the levels of circulating Ia.